Specific lectin bindings to oval cells and proliferated bile ductules

Histochemical evaluation of lectins was performed to examine the carbohydrate residues of oval cells induced by administration of α-naphthylisothiocyanate (ANIT), 2-acetylaminofluorene (2-AAF) and 3′-methyl-4-dimethylaminoazobenzene (3′-Me-DAB) in comparison with those of normal bile ducts and proliferated bile ductules induced by bile duct ligation. The normal bile ducts showed intense binding of Ricinus communis agglutinin, concanavalin A and wheat germ agglutinin, and weak binding of Ulex europaeus agglutinin I (UEA I). A few cells in the portal bile ducts showed binding of peanut agglutinin (PNA). Two different binding patterns were observed in oval cells and proliferated bile ductules. One group showed increased binding of PNA, while the other showed intense binding of UEA I. In both groups, binding of other lectins was similar to those of the normal bile duct. The first group included oval cells induced by 2-AAF and 3′-Me-DAB, and the second included both oval cells induced by ANIT and proliferated bile ductules induced by ligation. These results suggest that oval cells and proliferated bile ductules have their own specific carbohydrate residues and that oval cells induced by the carcinogens might be a cell population different from those induced by non-carcinogens and proliferated bile ductules by ligation. The authors wish to thank Dr. T. Itoshima and Dr. Y. Okada for their invaluable suggestions, and Mrs. T. Emi for her assistance in preparation of light microscopic examination.     

Distribution of light chains and ATPase activity of myosin in the atrioventricular conducting tissue of bovine heart

Summary The relations of the light chains of myosins of the atria, ventricles, and atrioventricular conducting tissue (specialized myocardial tissue) and the distribution of the light chains of myosin in different regions of the atrioventricular conducting tissue in bovine heart were examined. Two-dimensional gel electrophoresis showed that the atrial and ventricular myosins each had two light chains (LC₁ and LC₂). Ventricular LC₁ differed from atrial LC₁, but ventricular LC₂ corresponded to atrial LC₂. The specialized myocardial tissue myosin had three light chains (named here SL₁, SL₂, and SL₃). SL₁ comigrated with ventricular LC₁, SL₂ with atrial LC₁, and SL₃ with ventricular LC₂ and atrial LC₂. The compositions of the three light chains of myosins in various regions of the atrioventricular conducting tissue were determined by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. The percentage proportion of SL₁ decreased in the order—atrioventricular node (AVN), right and left bundle branches (RLBB), His bundle (HIS), false tendon (FT) myosin; while the percentage proportion of SL₂ decreased in the order—FT and HIS, RLBB, AVN myosin. The percentages of SL₃ in these four regions were similar. The Ca²⁺-activated ATPase activity of myosin was highest in the AVN and lowest in the FT. The activities in the HIS and RLBB were intermediate between those in the AVN and FT. Thus, the composition of the light chains and the Ca²⁺-activated ATPase activity were different in various regions of the atrioventricular conducting tissue.     

Reduced expression of heme oxygenase-1 in patients with coronary atherosclerosis.

Heme oxigenase-1 (HO-1) is known to be an inducible cytoprotective enzyme that copes with oxidative stress. However, changes in HO-1 expression and their association with human diseases have not been studied. To test the hypothesis that the capacity to upregulate HO-1 in response to oxidative stress is an intrinsic marker for susceptibility to coronary atherosclerosis, we assessed stimulation-induced change in HO-1 expression in blood cells in 110 patients who underwent coronary angiography, comparing the results with the extent of coronary atherosclerosis and (GT)(n) repeat polymorphism in the HO-1 gene promoter region, which is believed to affect the gene expression level. The extent of coronary atherosclerosis was assessed by coronary score. Mononuclear cells were incubated with 10 micromol/l hemin or vehicle for 4 h to maximally stimulate HO-1 expression, then the HO-1 expression level was determined by real-time polymerase chain reaction (PCR). The difference between the HO-1 mRNA levels of hemin- and vehicle-treated cells (DeltaHO-1 mRNA) was taken as an index of the capacity to upregulate HO-1 mRNA. The coefficient of variance of DeltaHO-1 mRNA was 7.2%. Consistent with previous studies, DeltaHO-1 mRNA was significantly lower in patients carrying a long (GT)(n) repeat. DeltaHO-1 mRNA negatively and significantly correlated with the coronary score (r(2)=0.50, p<0.01). In conclusion, the capacity to upregulate HO-1 expression may be determined, at least in part, by genetics, and reduced ability to induce HO-1 may be involved in the mechanism of coronary atherosclerosis.     

Mixed connective tissue disease with interstitial pneumonia in HTLV-1 carrier: case report and review of the literature

We report on a carrier of human T-lymphotropic virus type 1 (HTLV-1) who developed mixed connective tissue disease (MCTD). This patient suddenly manifested clinical symptoms and interstitial pneumonia ascribable to MCTD following long-term infection with HTLV-1. After initiation of oral prednisolone all manifestations quickly improved in parallel with a decrease in inflammatory reactions. In this patient HTLV-1 infection might have played an important role in the pathogenesis of MCTD. Since HTLV-1 can cause adult T-cell leukemia and HTLV-1-associated myelopathy, and also collagen diseases including MCTD, careful observation is necessary even in a carrier, particularly when autoantibodies are detectable in serum.     

Elderly-onset anticentromere antibody-positive pulmonary-renal syndrome: report of an autopsy case]

We report an autopsy case of elderly-onset anticentromere antibody-positive pulmonary-renal syndrome. An 84-year-old woman was admitted to our hospital with complaints of leg edema and general malaise. Neither skin rush nor arthritis was seen. Because of hematuria, proteinuria with various casts, renal dysfunction and anemia, a clinically diagnosis of rapidly progressive glomerulonephritis was made. Slight pulmonary hypertension was observed in ultrasonic cardiography. Hypocomplementemia was not seen. Tests for MPO- and PR 3-anti-neutrophil cytoplasmic antibodies and anti-glomerular basement membrane antibody were negative, but a high titer of antinuclear antibody with a discrete speckled pattern on immunofluorescent staining was disclosed. Results for anticentromere antibody and anti-Ki antibody were positive, but for anti-Sm antibody and anti-double stranded DNA antibody were both negative. She did not present any clinical features of systemic sclerosis or CREST syndrome. Subsequently, prednisolone was administered, but pulmonary alveolar hemorrhage occurred and the patient died of acute respiratory failure caused by massive pulmonary hemorrhage. Autopsy revealed crescentic glomerulonephritis including glomerular capillaritis and pulmonary capillaritis with positive granular deposits of immunoglobulins and compliment on the glomerular and pulmonary capillary walls. Immunologically mediated crescentic glomerulonephritis and pulmonary capillaritis was then diagnosed histopathologically. The main pathological feature of the case was small-vessel vasculitis with immune-complex deposition. Although this case did not fulfill the clinical criteria for systemic lupus erythematosus (SLE), its histological features resembled those of lupus nephritis and acute lupus pneumonitis. We speculated that anticentromere antibody-positive pulmonary-renal syndrome without any other symptoms or signs of connective tissue disease, such as our case, is a clinical entity distinct from typical SLE or CREST syndrome.     

Rapid and prominent up-regulation of high-affinity receptor for immunoglobulin G (Fc gamma RI) by cross-linking of beta 2 integrins on polymorphonuclear leukocytes

Receptors for the Fc region (FcR) of immunoglobulin (Ig)G play essential roles in effector functions of polymorphonuclear leukocytes (PMNs) including the antibody-mediated clearance of microbes. In contrast to the constitutive expression of the low-affinity receptors for IgG (Fc gamma RII [CD32] and Fc gamma RIII [CD16]), the high-affinity receptor Fc gamma RI (CD64) is barely detectable on unactivated PMNs. CD64 expression is induced in a slow kinetic manner by interferon (IFN)-gamma and granulocyte colony-stimulating factor (G-CSF) after 12 to 24 hours of exposure to these agents. We found that the cross-linking of CD11b as well as of CD18 induced comparable rapid increases in CD64 expression on the surface of PMNs, occurring within 15 minutes of exposure. Cross-linking of neither CD11a nor CD11c induced CD64 expression. In contrast to slow induction by IFN-gamma and G-CSF, the integrin-induced rapid CD64 expression did not require RNA synthesis. Genistein, herbimycin A, and 1,2-bis(o-aminophenoxy)ethan-N,N-N',N'-tetraacetic acid blocked the immediate expression of CD64 in a dose-dependent manner, suggesting that the signal is mediated through calcium mobilization and protein tyrosine kinase(s). Such rapid modulation of the high-affinity Fc gamma RI receptor by integrin cross-linking may reflect the requirement for rapid up-regulation of PMN effector functions, after interaction with endothelial cells, platelets or bacteria.     

Augmentation of human immunodeficiency virus type 1 gene expression by tumor necrosis factor alpha

It is now well established that cytokines are involved in the regulation of gene expression from HIV-1 LTR. The present study provides evidence that TNF-alpha stimulates HIV-1 gene expression and that the enhancer sequence within the HIV-1 LTR is involved in the stimulation. These results support the idea that immunologic stimulation and infection may trigger the development of clinical AIDS in individuals latently infected with HIV-1.     

Insulin-like growth factor I receptor blockade enhances chemotherapy and radiation responses and inhibits tumour growth in human gastric cancer xenografts

BACKGROUND AND AIMS: Insulin-like growth factor (IGF) I receptor (IGF-Ir) signalling is required for carcinogenicity and proliferation of many tumours but this pathway has not been studied in detail in gastric cancer. We have previously shown successful therapy for colorectal, pancreatic, and lung cancer using recombinant adenoviruses expressing dominant negative (dn) IGF-Ir. In this study, we sought to better dissect the role of IGF-Ir on progression of gastric cancer and determine whether IGF-Ir targeted adenoviruses represent potentially effective therapeutics for human gastric cancer. METHODS: We assessed the effect of IGF-Ir ligands on proliferation and survival in gastric cancer cells in culture. Then, recombinant adenoviruses expressing truncated IGF-Ir (482 and 950 amino acids long, IGF-Ir/dn) that function as dn inhibitors were studied in the treatment of human gastric cancer xenografts. We characterised the effects of IGF-Ir/dn on signalling blockade, growth, apoptosis induction, and in vivo therapeutic efficacy. RESULTS: IGF-Ir signalling promoted tumour growth and survival in gastric cancer. IGF-Ir/dn expression suppressed tumorigenicity both in vitro and in vivo and upregulated stressor induced apoptosis. IGF-Ir/dn blocked Akt-1 activation induced by IGF-I, IGF-II, and des(1-3)IGF-I, but not by insulin. IGF-Ir/dn expression increased radiation and chemotherapy induced apoptosis and the combination of IGF-Ir/dn and chemotherapy was very effective against tumours in mice. In an intraperitoneal model, IGF-Ir/dn therapy also suppressed peritoneal dissemination. CONCLUSIONS: IGF-Ir is involved in the regulation of survival and cell growth in human gastric cancer and may be a good molecular therapeutic target. Adenovirus-IGF-Ir/dn may thus have therapeutic use in gastric cancer.